Jonathan Higgins

Professor Jonathan Higgins

Research Fellow

Organisation

Newcastle University

Research summary

Inaccurate transmission of chromosomes from mother to daughter cells during cell division has profoundly deleterious consequences. For example, if normal cells produce daughter cells with an incorrect chromosome complement, then cell death is likely to occur. In rare cases such cells may survive and divide further, producing highly abnormal cells typical of many cancers. Additionally, if eggs receive an incorrect number of chromosomes, then infertility or birth defects can occur. Conversely, because cell division is a prerequisite for tumour growth, using drugs to deliberately interfere with it provides an opportunity for cancer therapy. Knowledge in this area is therefore vital to understand a variety of diseases, and to develop methods to prevent and treat them.

To accomplish cell division with high fidelity requires many changes to chromosome structure, including the displacement of proteins that might hinder chromosome segregation, and the recruitment of proteins that allow the chromosomes to be condensed, aligned and sorted into daughters. Throughout all of this, the chromosomes retain markers that remember which genes are on and which are off so that the cell can return to its original state once division is complete. My laboratory studies how these events are controlled in location and timing. In particular, chemical modifications are made to chromosomes by enzymes known as kinases during cell division. These modifications help determine where and when key regulatory factors bind to chromosomes. We want to find out how modification of core chromosomal proteins known as histones controls cell division, how this process contributes to cancer and birth defects, and how it can be exploited for disease therapy.